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Epigenetic regulation of cardiac regeneration after injury.

Objective

Cardiovascular disease is a leading cause of morbidity and mortality worldwide, and there is a constant and urgent need for novel, more effective therapies to treat it. Chronic tissue hypoxia, nutrient deprivation and myocardial cell death are some of the factors contributing to ischemic heart disease (IHD), the most common cause of death from all cardiovascular diseases. Current therapeutic approaches are limited in their capacity to enhance cardiac regeneration after injury. Toward novel selective therapies, it is important to gain a detailed understanding of pathways orchestrating cardiomyocyte proliferation during development and after injury.

This proposal aims to map the epigenetic landscape of cardiomyocytes at key stages of postnatal cardiomyocyte maturation, using the assay for transposase accessible chromatin with high-throughput sequencing (ATAC-Seq). The application of this novel technique to cardiomyocyte biology will allow for the identification of epigenetic mechanisms that drive cell cycle withdrawal during cardiomyocyte maturation. My pilot experiments indicate that the SWI/SNF chromatin remodeling factor Arid1a may prevent efficient cardiac regeneration after injury. The role of Arid1a during cardiomyocyte maturation will be characterized. Furthermore, I will examine if suppression of Arid1a in adult mouse heart can improve cardiac function and enhance regeneration after injury.

Mapping the epigenetic landscape of developing and mature cardiomyocytes represents an important step toward understanding the obstacles to efficient myocardial regeneration. Manipulation of Arid1a in diseased hearts may provide novel therapeutic approaches to enhance cardiac regeneration post ischemic injury.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-RI - RI – Reintegration panel

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 177 598,80
Address
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Netherlands

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 177 598,80
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